Modelling a two-peak enterovirus A71 outbreak caused in Ho Chi Minh City, Vietnam, in 2023.

Background: A hand-foot-and-mouth disease (HFMD) severe outbreak stroke Ho Chi Minh in 2023, with two successive peaks in incidence in July and September. Laboratory analyses showed that both peaks were caused by enterovirus A71 (EV-A71) subgenogroup B5 lineage. We consider 3 hypotheses that could explain this pattern: (i) the peaks are caused by cases from locations (ii) the 2 successive peaks reflect the spread of the virus across age classes (iii) the period from July to August coincides with summer break characterized by a drop in the contact rate. Methods: The line listing data with 43,380 HFMD cases in Ho Chi Minh City in 2023 were obtained from Ho Chi Minh City Center for Disease Control (HCDC). We will look at the epidemic curves per commune and/or district for testing the first hypothesis. To analyze age structure, we will look at the age distribution of cases as a function of time either continuous variable or binary variable (first peak and second peak), and space (commune or district). For age structure analysis with continuous time variables, we will analyze with the sliding window technique to compute how the median age and quantiles vary over time. We will use the time-series SIR (tSIR) model to estimate the pool of susceptible and the contact rate for testing our third hypothesis regarding the 2-peaks pattern being driven by the levels of susceptible in the population and the contact rate between the individuals in the population.

HFMD data from 2017 - 2023

Time - series epidemic curve of HFMD in Ho Chi Minh from 2017 - 2023

Epidemic curve of HFMD in Ho Chi Minh (you can double - click on the legend to display a specific year)

Data description

Characteristic 2013
N = 8,0781
2014
N = 10,0431
2015
N = 8,7291
2016
N = 5,7401
2017
N = 30,8251
2018
N = 39,3521
2019
N = 28,4861
2020
N = 16,3981
2021
N = 9,7721
2022
N = 19,1651
2023
N = 43,3801
2024
N = 7,3971
Age NA (NA, NA) NA (NA, NA) NA (NA, NA) NA (NA, NA) 1.84 (1.21, 2.80) 1.95 (1.22, 3.04) 1.85 (1.18, 2.90) 1.83 (1.18, 2.79) 2.21 (1.42, 3.28) 2.25 (1.48, 3.29) 2.54 (1.68, 3.72) 2.35 (1.38, 3.54)
Gender











    Female 3,159 (39%) 4,070 (41%) 3,617 (41%) 2,391 (42%) 12,982 (42%) 16,815 (43%) 12,196 (43%) 6,944 (42%) 4,123 (42%) 7,950 (41%) 18,461 (43%) 3,121 (42%)
    Male 4,919 (61%) 5,973 (59%) 5,112 (59%) 3,349 (58%) 17,843 (58%) 22,537 (57%) 16,290 (57%) 9,454 (58%) 5,649 (58%) 11,215 (59%) 24,919 (57%) 4,276 (58%)
District











    1 157 (1.9%) 174 (1.7%) 156 (1.8%) 96 (1.7%) 632 (2.1%) 688 (1.7%) 592 (2.1%) 278 (1.7%) 163 (1.7%) 383 (2.0%) 707 (1.6%) 121 (1.6%)
    10 240 (3.0%) 270 (2.7%) 234 (2.7%) 145 (2.5%) 912 (3.0%) 944 (2.4%) 813 (2.9%) 265 (1.6%) 226 (2.3%) 492 (2.6%) 947 (2.2%) 149 (2.0%)
    11 272 (3.4%) 343 (3.4%) 282 (3.2%) 210 (3.7%) 836 (2.7%) 937 (2.4%) 692 (2.4%) 347 (2.1%) 272 (2.8%) 434 (2.3%) 984 (2.3%) 149 (2.0%)
    12 398 (4.9%) 590 (5.9%) 422 (4.8%) 266 (4.6%) 2,006 (6.5%) 2,391 (6.1%) 1,967 (6.9%) 1,198 (7.3%) 554 (5.7%) 1,243 (6.5%) 3,108 (7.2%) 534 (7.2%)
    3 148 (1.8%) 174 (1.7%) 187 (2.1%) 102 (1.8%) 684 (2.2%) 708 (1.8%) 631 (2.2%) 290 (1.8%) 175 (1.8%) 420 (2.2%) 693 (1.6%) 107 (1.4%)
    4 184 (2.3%) 205 (2.0%) 204 (2.3%) 114 (2.0%) 707 (2.3%) 784 (2.0%) 642 (2.3%) 435 (2.7%) 233 (2.4%) 561 (2.9%) 771 (1.8%) 138 (1.9%)
    5 250 (3.1%) 289 (2.9%) 238 (2.7%) 127 (2.2%) 648 (2.1%) 690 (1.8%) 533 (1.9%) 212 (1.3%) 168 (1.7%) 380 (2.0%) 630 (1.5%) 120 (1.6%)
    6 426 (5.3%) 438 (4.4%) 437 (5.0%) 270 (4.7%) 1,196 (3.9%) 1,383 (3.5%) 1,006 (3.5%) 534 (3.3%) 415 (4.2%) 579 (3.0%) 1,212 (2.8%) 224 (3.0%)
    7 302 (3.7%) 347 (3.5%) 301 (3.4%) 188 (3.3%) 1,474 (4.8%) 1,654 (4.2%) 1,316 (4.6%) 724 (4.4%) 423 (4.3%) 929 (4.8%) 1,950 (4.5%) 321 (4.3%)
    8 793 (9.8%) 883 (8.8%) 803 (9.2%) 706 (12%) 2,310 (7.5%) 2,427 (6.2%) 1,718 (6.0%) 1,037 (6.3%) 738 (7.6%) 1,352 (7.1%) 2,400 (5.5%) 476 (6.4%)
    Bình Chánh 832 (10%) 909 (9.1%) 919 (11%) 541 (9.4%) 2,056 (6.7%) 4,343 (11%) 2,225 (7.8%) 2,116 (13%) 1,334 (14%) 1,111 (5.8%) 4,804 (11%) 965 (13%)
    Bình Tân 737 (9.1%) 1,051 (10%) 839 (9.6%) 554 (9.7%) 2,771 (9.0%) 4,850 (12%) 2,912 (10%) 1,999 (12%) 1,455 (15%) 1,544 (8.1%) 4,602 (11%) 795 (11%)
    Bình Thạnh 315 (3.9%) 310 (3.1%) 248 (2.8%) 149 (2.6%) 1,435 (4.7%) 1,818 (4.6%) 1,417 (5.0%) 774 (4.7%) 385 (3.9%) 1,026 (5.4%) 1,967 (4.5%) 335 (4.5%)
    Cần Giờ 74 (0.9%) 89 (0.9%) 36 (0.4%) 32 (0.6%) 334 (1.1%) 275 (0.7%) 304 (1.1%) 96 (0.6%) 42 (0.4%) 186 (1.0%) 477 (1.1%) 57 (0.8%)
    Củ Chi 299 (3.7%) 517 (5.1%) 614 (7.0%) 477 (8.3%) 1,898 (6.2%) 1,579 (4.0%) 1,163 (4.1%) 537 (3.3%) 425 (4.3%) 936 (4.9%) 1,966 (4.5%) 388 (5.2%)
    Gò Vấp 352 (4.4%) 529 (5.3%) 389 (4.5%) 228 (4.0%) 1,551 (5.0%) 1,806 (4.6%) 1,423 (5.0%) 822 (5.0%) 324 (3.3%) 996 (5.2%) 2,616 (6.0%) 412 (5.6%)
    Hóc Môn 460 (5.7%) 613 (6.1%) 449 (5.1%) 255 (4.4%) 1,675 (5.4%) 1,961 (5.0%) 1,408 (4.9%) 727 (4.4%) 424 (4.3%) 914 (4.8%) 2,037 (4.7%) 334 (4.5%)
    Nhà Bè 197 (2.4%) 232 (2.3%) 173 (2.0%) 154 (2.7%) 866 (2.8%) 1,106 (2.8%) 933 (3.3%) 480 (2.9%) 249 (2.5%) 713 (3.7%) 1,434 (3.3%) 260 (3.5%)
    Phú Nhuận 120 (1.5%) 157 (1.6%) 87 (1.0%) 62 (1.1%) 412 (1.3%) 545 (1.4%) 442 (1.6%) 241 (1.5%) 123 (1.3%) 398 (2.1%) 628 (1.4%) 85 (1.1%)
    Tân Bình 456 (5.6%) 440 (4.4%) 339 (3.9%) 194 (3.4%) 1,582 (5.1%) 1,764 (4.5%) 1,368 (4.8%) 581 (3.5%) 362 (3.7%) 975 (5.1%) 1,837 (4.2%) 245 (3.3%)
    Tân Phú 363 (4.5%) 502 (5.0%) 493 (5.6%) 315 (5.5%) 1,673 (5.4%) 2,293 (5.8%) 1,542 (5.4%) 740 (4.5%) 528 (5.4%) 1,068 (5.6%) 2,340 (5.4%) 316 (4.3%)
    Thủ Đức 703 (8.7%) 981 (9.8%) 879 (10%) 555 (9.7%) 3,167 (10%) 4,406 (11%) 3,439 (12%) 1,965 (12%) 754 (7.7%) 2,525 (13%) 5,270 (12%) 866 (12%)
Treatment











    Death 2 (<0.1%) 1 (<0.1%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
    Discharge 0 (0%) 0 (0%) 0 (0%) 0 (0%) 4,817 (16%) 5,245 (13%) 2,427 (8.5%) 1,111 (6.8%) 488 (5.0%) 871 (4.5%) 1,174 (2.7%) 299 (4.0%)
    Inpatient 8,076 (100%) 10,042 (100%) 8,729 (100%) 5,740 (100%) 510 (1.7%) 1,805 (4.6%) 1,702 (6.0%) 1,585 (9.7%) 1,219 (12%) 1,355 (7.1%) 5,598 (13%) 949 (13%)
    Others 0 (0%) 0 (0%) 0 (0%) 0 (0%) 9 (<0.1%) 3 (<0.1%) 0 (0%) 0 (0%) 0 (0%) 2 (<0.1%) 11 (<0.1%) 2 (<0.1%)
    Outpatient 0 (0%) 0 (0%) 0 (0%) 0 (0%) 25,483 (83%) 32,281 (82%) 24,350 (85%) 13,692 (83%) 8,063 (83%) 16,920 (88%) 36,540 (84%) 6,140 (83%)
    Transfer 0 (0%) 0 (0%) 0 (0%) 0 (0%) 6 (<0.1%) 18 (<0.1%) 7 (<0.1%) 10 (<0.1%) 2 (<0.1%) 17 (<0.1%) 57 (0.1%) 7 (<0.1%)
1 Median (Q1, Q3); n (%)

First hypothesis

Epicurve

We will look at the epidemic curves per commune and/or district whether cases from locations cause the peaks

Geographical differences testing

The Chi-square test was used for testing the case proportion between two peaks of each district compared to others.Districts in the North and North-East likely contributed to the first peak and the Southern contributed to the second peak.

Second hypothesis

To analyze age structure, we will look at the age distribution of cases as a function of time either continuous variable or binary variable (first peak and second peak), and space (commune or district).

Binary time variable

Characteristic 1st peak
N = 20,3581
2nd peak
N = 23,0141
age 2.649 (1.784, 3.726) 2.393 (1.548, 3.721)
1 Median (Q1, Q3)

Continuous time variable

Two types of analysis: heat map and sliding window (time-varying mean age and [25th,75th] quartile).

Full period analysis

Sliding window with width 7 days and step 1 days

Heat map of age distribution (sliding window with 7-day width and 7-day step)

Annual analysis

Spatial distribution

Attack rate using population census 2019 data

Attack rate using data from vaccine registry (Hep B)

Epiestim

Using Cori method to estimate Instantaneous reproduction number \(R_t^i\)

Use reconstructed incidence to fit

Use aggregated incidence to fit

tSIR

[1] "gaussian regressian failed -- switching to loess regression"
           alpha        mean beta         mean rho         mean sus 
        6.90e-01         7.62e-05         1.03e+00         9.46e+04 
prop. init. sus. prop. init. inf. 
        7.54e-03         6.05e-06 

Attack rate

\[\text{Attack rate} = \frac{\text{number of new cases in the population at risk}}{\text{number of people at risk in the population}}\]

Reconstruct epicure 2013-2023

HAND, FOOT AND MOUTH DISEASE IN SOUTHERN VIETNAM DURING 2015 – 2021

Clinical, etiological and epidemiological investigations of hand, foot and mouth disease in southern Vietnam during 2015 – 2018